Cellectis Presents Multiple Strategies to Enhance CAR T-cell Efficacy in Solid Tumors at the SITC Annual Meeting
Cellectis announced pre-clinical data presentation at SITC's 39th Annual Meeting, showcasing strategies to enhance CAR T-cell efficacy against solid tumors. The research focuses on overcoming challenges in the tumor microenvironment (TME) using TALEN®-mediated gene editing to generate allogeneic CAR T-cells. The company developed two key approaches: a FAP-dependent expression system to limit cytotoxic activity to tumor areas, and integration of IL-12 into PD-1 regulatory elements while inactivating TGFBR2. These strategies showed enhanced T-cell proliferation and infiltration while reducing tumor burden and limiting side effects, potentially offering new therapeutic options for solid tumor patients.
Cellectis ha annunciato la presentazione di dati pre-clinici durante il 39° Meeting Annuale della SITC, evidenziando strategie per migliorare l'efficacia delle cellule T CAR contro i tumori solidi. La ricerca si concentra sul superamento delle sfide nel microambiente tumorale (TME) utilizzando l'editing genetico mediato da TALEN® per generare cellule T CAR allogeneiche. L'azienda ha sviluppato due approcci chiave: un sistema di espressione dipendente da FAP per limitare l'attività citotossica alle aree tumorali, e l'integrazione di IL-12 negli elementi regolatori di PD-1 mentre inattiva TGFBR2. Queste strategie hanno mostrato un aumento della proliferazione e dell'infiltrazione delle cellule T, riducendo il carico tumorale e limitando gli effetti collaterali, potenzialmente offrendo nuove opzioni terapeutiche per i pazienti con tumori solidi.
Cellectis anunció la presentación de datos preclínicos en la 39ª Reunión Anual de la SITC, mostrando estrategias para mejorar la eficacia de las células T CAR contra tumores sólidos. La investigación se centra en superar los desafíos en el microambiente tumoral (TME) utilizando la edición genética mediada por TALEN® para generar células T CAR alogénicas. La empresa desarrolló dos enfoques clave: un sistema de expresión dependiente de FAP para limitar la actividad citotóxica a las áreas tumorales, y la integración de IL-12 en los elementos reguladores de PD-1 mientras inactiva TGFBR2. Estas estrategias mostraron una mayor proliferación e infiltración de células T, reduciendo la carga tumoral y limitando los efectos secundarios, lo que podría ofrecer nuevas opciones terapéuticas para pacientes con tumores sólidos.
Cellectis는 SITC 제39회 연례 회의에서 발표할 전임상 데이터를 발표하며 고형 종양에 대한 CAR T 세포의 효능을 강화하기 위한 전략을 선보였습니다. 연구는 TALEN® 매개 유전자 편집을 사용하여 반응성 CAR T 세포를 생성하는 데 있어 종양 미세 환경 (TME)에서의 도전을 극복하는 데 중점을 둡니다. 회사는 두 가지 주요 접근 방식을 개발했습니다: 종양 영역에서의 세포 독성을 제한하기 위한 FAP 의존성 발현 시스템과 TGFBR2를 비활성화하면서 PD-1 조절 요소에 IL-12를 통합하는 것입니다. 이러한 전략은 T 세포의 증식과 침윤이 향상되며 종양 부담을 줄이고 부작용을 제한하여 고형 종양 환자에게 새로운 치료 옵션을 제공할 가능성이 있습니다.
Cellectis a annoncé la présentation de données précliniques lors de la 39ème réunion annuelle de la SITC, mettant en avant des stratégies pour améliorer l'efficacité des cellules T CAR contre les tumeurs solides. La recherche se concentre sur le surmontement des défis dans le microenvironnement tumoral (TME) en utilisant l'édition génomique médiée par TALEN® pour générer des cellules T CAR allogéniques. L'entreprise a développé deux approches clés : un système d'expression dépendant de FAP pour limiter l'activité cytotoxique aux zones tumorales, et l'intégration de l'IL-12 dans les éléments régulateurs de PD-1 tout en inactivant TGFBR2. Ces stratégies ont montré une augmentation de la prolifération et de l'infiltration des cellules T tout en réduisant la charge tumorale et en limitant les effets secondaires, offrant potentiellement de nouvelles options thérapeutiques pour les patients atteints de tumeurs solides.
Cellectis kündigte die Präsentation präklinischer Daten auf dem 39. Jahrestreffen der SITC an und stellte Strategien vor, um die Wirksamkeit von CAR-T-Zellen gegen solide Tumore zu verbessern. Die Forschung konzentriert sich darauf, Herausforderungen im tumoralen Mikroumfeld (TME) zu überwinden, indem TALEN®-vermittelte Genbearbeitung eingesetzt wird, um allogene CAR-T-Zellen zu erzeugen. Das Unternehmen entwickelte zwei wesentliche Ansätze: ein FAP-abhängiges Expressionssystem, das die zytotoxische Aktivität auf Tumorgebiete beschränkt, sowie die Integration von IL-12 in die PD-1-regulatorischen Elemente, während TGFBR2 inaktiviert wird. Diese Strategien zeigten eine verbesserte Proliferation und Infiltration von T-Zellen und reduzierten die Tumorlast sowie Nebenwirkungen, was potenziell neue therapeutische Optionen für Patienten mit soliden Tumoren bieten könnte.
- Pre-clinical data shows enhanced CAR T-cell activity in solid tumors
- Demonstrated reduction in tumor burden while limiting side effects
- Successfully developed dual approach strategy for targeting solid tumors
- None.
Insights
The presentation of preclinical data for enhanced CAR T-cell therapies targeting solid tumors represents incremental progress but lacks immediate market impact. While the research shows promising strategies to overcome key challenges in solid tumor treatment, including the hostile tumor microenvironment and potential toxicity issues, these are still early-stage findings without clinical validation.
The integration of IL-12 and TALEN gene editing technology demonstrates technical advancement, but several similar approaches are being pursued by competitors. The market impact will remain until these innovations show clinical efficacy in human trials. For investors, this represents ongoing R&D progress but does not materially change the company's near-term prospects or valuation.
NEW YORK, Nov. 05, 2024 (GLOBE NEWSWIRE) -- Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today that pre-clinical data to enhance CAR T cell activity against solid tumors while preventing potential toxicity, will be presented at the Society for Immunotherapy of Cancer’s 39th Annual Meeting (SITC), that will take place on November 6-10, 2024 in Houston, Texas.
The data will be presented in a poster:
Title: Breaking barriers in solid tumors with SMART allogeneic CAR T-cells
Date / Time: November 9th, 2024 from 9:00am to 8:30pm ET
Presenter: Beatriz Aranda-Orgilles, Associate Director, Immuno Oncology at Cellectis
Poster number: 254
Despite the success of CAR T-cell therapies treating blood cancers, these cutting-edge technologies continue to face obstacles in solid tumors. A main barrier is the hostile tumor microenvironment (TME), which forms an immunosuppressive barrier and restricts T-cell infiltration into the tumor. Other contributing causes such as tumor antigen diversity or low expression of CAR-targeted tumor-associated antigens (TAA) in normal tissues can lead to antigen escape or on-target off-tumor toxicity, respectively. These factors can lead to relapse and pose a challenge for therapeutic safety.
Cellectis presents several strategies using TALEN®-mediated gene editing to generate allogeneic CAR T-cells while repurposing PD-1 function with tightly regulated functionalities, with the objective to increase efficacy and avoid potential toxicities in solid tumors.
Using in vitro and in vivo techniques, we show that TME-induced FAP-dependent expression of CAR tethers cytotoxic activity to the tumor area and can minimize potential "on-target off-tumor" toxicities. In a parallel approach, we integrate IL-12 into PD-1 regulatory elements to confine IL-12 to the TME and inactivate TGFBR2 to overcome TGFB1-mediated resistance. This strategy enhances proliferation and infiltration of CAR T-cells, while reducing tumor burden and limiting side effects.
Overall, our data show the potential of repurposing immune pathways to create armored allogeneic CAR T-cells with enhanced activity in immunosuppressive microenvironments while minimizing potential safety issues. These approaches have the potential to provide a therapeutic option for patients with solid malignancies.
The poster is available on Cellectis website
About Cellectis
Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with 25 years of experience and expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN®, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. Cellectis’ headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS).
To find out more, visit our website: www.cellectis.com
Follow Cellectis on social networks @cellectis on LinkedIn and X (formerly Twitter)
TALEN® is a registered trademark owned by Cellectis.
Forward-looking Statements
This press release contains “forward-looking” statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as "can”, “has the potential to” and emerging or the negative of these and similar expressions. These forward-looking statements, which are based on our management’s current expectations and assumptions and on information currently available to management, include statements about the potential of our research programs. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including with respect to the numerous risks associated with biopharmaceutical product candidate development. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and the financial report (including the management report) for the year ended December 31, 2023 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.
For further information on Cellectis, please contact:
Media contacts:
Pascalyne Wilson, Director, Communications, + 33 (0)7 76 99 14 33, media@cellectis.com
Patricia Sosa Navarro, Chief of Staff to the CEO, +33 (0)7 76 77 46 93
Investor Relations contact:
Arthur Stril, Interim Chief Financial Officer, investors@cellectis.com
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FAQ
What new CAR T-cell strategies did Cellectis (CLLS) present at SITC 2024?
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